The obstructive sleep apnea syndrome (OSAS) is a common cause of morbidity in the pediatric population This proposal will integrate studies of neuromotor control of the upper airway (UA) and UA structure in order to provide a comprehensive assessment of all pathophysiologic risk factors for OSAS in the same individual, and to apply this knowledge to high risk pediatric patients. The proposal focuses on the effects of obesity during the transitional period of adolescence. The overall hypothesis is that OSAS develops when a structural load is acquired by an individual with an underlying impairment of UA neuromotor function. This will be a 1:1:1 matched case-dual control study with a complementary interventional component. UA reflexes will be determined by measuring the difference between the UA pressure-flow response during sleep in the activated vs the hypotonic state, and the UA response to hypercapnia. UA size and structure will be determined using MRI. In Aim 1, we will determine the contribution of UA reflexes to the apnea hypopnea index (AHI) by conducting a cross-sectional, case control study that will compare obese, adolescent cases with OSAS to (i) non-snoring, BMI-matched obese controls and to (ii) non-obese, non-snoring controls. We hypothesize that UA reflexes will be decreased in obese adolescents with OSAS compared to obese controls, and that UA reflexes will be greater in obese controls than in non-obese controls. In Aim 2A, we will determine the contribution of structural UA narrowing to the AHI. We hypothesize that the UA will be narrower in obese adolescents with OSAS compared to obese controls. In Aim 2B, we will identify the most important structural factors leading to upper airway narrowing. We hypothesize that adenotonsillar tissue and regional distribution of adipose tissue are the prime determinants of UA size in adolescents. In Aim 3, we will determine the effects of weight loss on OSAS. In Aim 3A, we will determine whether the degree of weight loss correlates with the change in AHI. We hypothesize that the greater the weight loss, the greater the fall in AHI. In Aim 3B, we will determine whether the decrease in AHI following weight loss is due primarily to a change in UA reflexes or a change in UA size. We hypothesize that the improvement in AHI following weight loss is due primarily to an increase in UA size rather than to a change in UA reflexes. In Aim 3C, we will determine the effect of weight loss on UA structure. We hypothesize that weight loss will result primarily in a decrease in the size of the parapharyngeal fat pads, but may also affect tongue and soft palate size. These studies will help elucidate the pathophysiology of OSAS in obese adolescents, ultimately resulting in improved management of this disease. PUBLIC HEALTH RELEVANCE: The current obesity epidemic in the United States is resulting in an increasing prevalence of the obstructive sleep apnea syndrome (OSAS) in adolescents. This study will help elucidate of the causes of OSAS in teenagers, and determine the effectiveness of weight loss in ameliorating these causative factors.